Transcatheter Aortic Valve Replacement in Bicuspid Aortic Valve Stenosis.

After 15 years of successive randomized, controlled trials, indications for transcatheter aortic valve replacement (TAVR) are rapidly expanding. In the coming years, this procedure could become the first line treatment for patients with a symptomatic severe aortic stenosis and a tricuspid aortic valve anatomy. However, randomized, controlled trials have excluded bicuspid aortic valve (BAV), which is the most frequent congenital heart disease occurring in 1% to 2% of the total population and representing at least 25% of patients 80 years of age or older referred for aortic valve replacement. The use of a less invasive transcatheter therapy in this elderly population became rapidly attractive, and approximately 10% of patients currently undergoing TAVR have a BAV. The U.S. Food and Drug Administration and the "European Conformity" have approved TAVR for low-risk patients regardless of the aortic valve anatomy whereas international guidelines recommend surgical replacement in BAV populations. Given this progressive expansion of TAVR toward younger and lower-risk patients, heart teams are encountering BAV patients more frequently, while the ability of this therapy to treat such a challenging anatomy remains uncertain. This review will address the singularity of BAV anatomy and associated technical challenges for the TAVR procedure. We will examine and summarize available clinical evidence and highlight critical knowledge gaps regarding TAVR utilization in BAV patients. We will provide a comprehensive overview of the role of computed tomography scans in the diagnosis, and classification of BAV and TAVR procedure planning. Overall, we will offer an integrated framework for understanding the current role of TAVR in the treatment of bicuspid aortic stenosis and for guiding physicians in clinical decision-making.

Long-term follow-up after ultrathin vs. conventional 2nd-generation drug-eluting stents: a systematic review and meta-analysis of randomized controlled trials.

AIMS: Contemporary 2nd-generation thin-strut drug-eluting stents (DES) are considered standard of care for revascularization of patients undergoing percutaneous coronary intervention. A previous meta-analysis of 10 randomized controlled trials (RCTs) with 11 658 patients demonstrated a 16% reduction in the 1-year risk of target lesion failure (TLF) with ultrathin-strut DES compared with conventional 2nd-generation thin-strut DES. Whether this benefit is sustained longer term is not known, and newer trial data may inform these relative outcomes. We therefore sought to perform an updated systematic review and meta-analysis of RCTs comparing clinical outcomes with ultrathin-strut DES (≤70 µm strut thickness) with conventional 2nd-generation thin-strut DES. METHODS AND RESULTS: We performed a random-effects meta-analysis of all RCTs comparing ultrathin-strut DES to conventional 2nd-generation thin-strut DES. The pre-specified primary endpoint was long-term TLF, a composite of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (CD-TLR). Secondary endpoints included the components of TLF, stent thrombosis (ST), and all-cause death. There were 16 eligible trials in which 20 701 patients were randomized. The weighted mean follow-up duration was 2.5 years. Ultrathin-strut DES were associated with a 15% reduction in long-term TLF compared with conventional 2nd-generation thin-strut DES [relative risk (RR) 0.85, 95% confidence interval (CI) 0.76-0.96, P = 0.008] driven by a 25% reduction in CD-TLR (RR 0.75, 95% CI 0.62-0.92, P = 0.005). There were no significant differences between stent types in the risks of MI, ST, cardiac death, or all-cause mortality. CONCLUSIONS: At a mean follow-up of 2.5 years, ultrathin-strut DES reduced the risk of TLF, driven by less CD-TLR compared with conventional 2nd-generation thin-strut DES, with similar risks of MI, ST, cardiac death, and all-cause mortality.

Efficacy and safety of intravascular lithotripsy for the treatment of peripheral arterial disease: An individual patient-level pooled data analysis.

BACKGROUND: Peripheral arterial disease (PAD) is one of the most common manifestations of atherosclerotic disease worldwide. Peripheral arterial calcification reduces acute success and long-term patency of endovascular therapy for PAD. Several calcium modification devices are available for use in peripheral interventions. Outcomes after peripheral intravascular lithotripsy (IVL), a novel approach using pulsatile sonic waves to treat luminal and medial calcium in patients with PAD, have not been extensively characterized. Therefore, we sought to perform an individual patient-level data (IPD) pooled analysis of available studies to evaluate the efficacy and safety of IVL in the treatment of PAD. METHODS AND RESULTS: We pooled IPD, including baseline and procedural variables, from five prospective studies which assessed IVL in the treatment of patients with extensive peripheral artery calcification. Final postprocedural percent diameter stenosis (%DS) and procedural angiographic complications were assessed by independent core laboratory. Efficacy endpoints were analyzed using linear mixed effects models and safety endpoints were tabulated overall and by vascular bed. Among 336 patients who underwent endovascular revascularization with use of IVL, there was a significant reduction between pre-procedural and final %DS of 55.1% (95% confidence interval 53.3-57.0%, p < .0001). Core-laboratory assessed lesion-level complications, including flow-limiting dissections (Types D-F), vessel perforation, distal embolization, thrombus, abrupt closure, and no reflow, occurred in 4/328 (1.22%) of treated lesions. CONCLUSIONS: The present IPD of five prospective studies, marking the largest analysis to date evaluating the use of IVL in significantly calcified PAD lesions, demonstrates this treatment strategy to be both effective and safe.

Incidence of cardiovascular events in patients with stabilized coronary heart disease: the EUROASPIRE IV follow-up study.

The EUROASPIRE surveys (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) demonstrated that most European coronary patients fail to achieve lifestyle, risk factor and therapeutic targets. Here we report on the 2-year incidence of hard cardiovascular (CV) endpoints in the EUROASPIRE IV cohort. EUROASPIRE IV (2012-2013) was a large cross-sectional study undertaken at 78 centres from selected geographical areas in 24 European countries. Patients were interviewed and examined at least 6 months following hospitalization for a coronary event or procedure. Fatal and non-fatal CV events occurring at least 1 year after this baseline screening were registered. The primary outcome in our analyses was the incidence of CV death or non-fatal myocardial infarction, stroke or heart failure. Cox regression models, stratified for country, were fitted to relate baseline characteristics to outcome. Our analyses included 7471 predominantly male patients. Overall, 222 deaths were registered of whom 58% were cardiovascular. The incidence of the primary outcome was 42 per 1000 person-years. Comorbidities were strongly and significantly associated with the primary outcome (multivariately adjusted hazard ratio HR, 95% confidence interval): severe chronic kidney disease (HR 2.36, 1.44-3.85), uncontrolled diabetes (HR 1.89, 1.50-2.38), resting heart rate ≥ 75 bpm (HR 1.74, 1.30-2.32), history of stroke (HR 1.70, 1.27-2.29), peripheral artery disease (HR 1.48, 1.09-2.01), history of heart failure (HR 1.47, 1.08-2.01) and history of acute myocardial infarction (HR 1.27, 1.05-1.53). Low education and feelings of depression were significantly associated with increased risk. Lifestyle factors such as persistent smoking, insufficient physical activity and central obesity were not significantly related to adverse outcome. Blood pressure and LDL-C levels appeared to be unrelated to cardiovascular events irrespective of treatment. In patients with stabilized CHD, comorbid conditions that may reflect the ubiquitous nature of atherosclerosis, dominate lifestyle-related and other modifiable risk factors in terms of prognosis, at least over a 2-year follow-up period.

Undetected dysglycaemia common in primary care patients treated for hypertension and/or dyslipidaemia: on the need for a screening strategy in clinical practice. A report from EUROASPIRE IV a registry from the EuroObservational Research Programme of the European Society of Cardiology.

BACKGROUND: Dysglycaemia defined as type 2 diabetes (T2DM) and impaired glucose tolerance (IGT), increases the risk of cardiovascular disease (CVD). The negative impact is more apparent in the presence of hypertension and/or dyslipidaemia. Thus, it seems reasonable to screen for dysglycaemia in patients treated for hypertension and/or dyslipidaemia. A simple screening algorithm would enhance the adoption of such strategy in clinical practice. OBJECTIVES: To test the hypotheses (1) that dysglycaemia is common in patients with hypertension and/or dyslipidaemia and (2) that initial screening with the Finnish Diabetes Risk Score (FINDRISC) will decrease the need for laboratory based tests. METHODS: 2395 patients (age 18-80 years) without (i) a history of CVD or TDM2, (ii) prescribed blood pressure and/or lipid lowering drugs answered the FINDRISC questionnaire and had an oral glucose tolerance test (OGTT) and HbA1c measured. RESULTS: According to the OGTT 934 (39%) had previously undetected dysglycaemia (T2DM 19%, IGT 20%). Of patients, who according to FINDRISC had a low, moderate or slightly elevated risk 20, 34 and 41% and of those in the high and very high-risk category 49 and 71% had IGT or T2DM respectively. The OGTT identified 92% of patients with T2DM, FPG + HbA1c 90%, FPG 80%, 2hPG 29% and HbA1c 22%. CONCLUSIONS: (1) The prevalence of dysglycaemia was high in patients treated for hypertension and/or dyslipidaemia. (2) Due to the high proportion of dysglycaemia in patients with low to moderate FINDRISC risk scores its initial use did not decrease the need for subsequent glucose tests. (3) FPG was the best test for detecting T2DM. Its isolated use is limited by the inability to disclose IGT. A pragmatic strategy, decreasing the demand for an OGTT, would be to screen all patients with FPG followed by OGTT in patients with IFG.

Cause-specific death in heart failure across the ejection fraction spectrum: A comprehensive assessment of over 100 000 patients in the Swedish Heart Failure Registry.

AIM: To assess cause-specific death in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction (HFpEF, HFmrEF, and HFrEF). METHODS AND RESULTS: Data were analysed from the Swedish Heart Failure Registry (SwedeHF) and the National Patient Register of patients enrolled in SwedeHF 2000-2021. Cox proportional hazards regression models were performed and adjusted for age, sex and time period. Among 100 584 patients (23% HFpEF, 23% HFmrEF, 53% HFrEF), median age (interquartile range) was 75 (66-82) and 36% were female. Of those who died within 5 years, most deaths were ascribed to cardiovascular (CV) causes across all ejection fraction (EF) categories. Within 5 years, HFpEF had higher adjusted risk of non-CV death (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.28-1.38, p < 0.001) and lower adjusted risk of CV death (HR 0.85, 95% CI 0.82-0.88, p < 0.001) compared to HFrEF. Ischaemic heart disease (IHD) and cancer were the most common causes of CV and non-CV death regardless of EF category. The incidence rate of CV death due to IHD was highest in HFrEF while incidence rates of CV death due to pulmonary vascular disease, stroke, valvular heart disease and atrial fibrillation increased with increasing EF. The incidence rates of non-CV deaths due to cancer, respiratory disease, and infections increased with increasing EF. CONCLUSION: Cardiovascular death was more common than non-CV death across all EF categories although the risk of non-CV death within 5 years was higher with increasing EF. IHD and cancer were the most common causes of CV and non-CV deaths, respectively, regardless of EF category.

Heart failure with preserved ejection fraction epidemiology, pathophysiology, diagnosis and treatment strategies.

The prevalence of HF with preserved ejection raction (HFpEF, with EF ≥50%) is increasing across all populations with high rates of hospitalization and mortality, reaching up to 80% and 50%, respectively, within a 5-year timeframe. Comorbidity-driven systemic inflammation is thought to cause coronary microvascular dysfunction and increased epicardial adipose tissue, leading to downstream friborsis and molecular changes in the cardiomyocyte, leading to increased stiffness and diastolic dynsfunction. HFpEF poses unique challenges in terms of diagnosis due to its complex and diverse nature. The diagnosis of HFpEF relies on a combination of clinical assessment, imaging studies, and biomarkers. An additional important step in diagnosing HFpEF involves excluding certain cardiac diagnoses that may be specific underlying causes of HFpEF or may be masquerading as HFpEF and require specific alternative treatment approaches. In addition to administering sodium-glucose cotransporter 2 inhibitors to all patients, the most effective approach to enhance clinical outcomes may involve tailored therapy based on each patient's unique clinical profile. Exercise should be recommended for all patients to improve the quality of life. Glucagon-like peptide-1 1 agonists are a promising treatment option in obese HFpEF patients. Novel approaches targeting inflammation are also in early phase trials.

Cholinesterase inhibitors are associated with reduced mortality in patients with Alzheimer's disease and previous myocardial infarction.

BACKGROUND: Cholinesterase inhibitors (ChEIs) are the first-line symptomatic pharmacologic treatment for patients with mild-to-moderate Alzheimer's disease (AD). Although the target organ for this group of drugs is the brain, inhibition of the enzyme may affect cardiac function through vagotonic and anti-inflammatory effects. OBJECTIVE: To assess the impact of ChEIs on outcomes in patients with AD who have experienced myocardial infarction (MI) prior to the AD diagnosis. METHODS: Patients who had experienced MI before they were diagnosed with AD or Alzheimer's mixed dementia between 2008 and 2018 were identified from the Swedish Dementia Registry (SveDem, www.svedem.se), which was linked to the National Patient Registry to obtain data on MI and mortality. Cox proportional hazards regression model among a propensity score-matched dataset was performed to assess the association between ChEI treatment and clinical outcomes. RESULTS: Of 3198 patients with previous MI and a diagnosis of AD or mixed dementia, 1705 (53%) were on treatment with ChEIs. Patients treated with ChEIs were more likely to be younger and have a better overall cardiovascular (CV) risk profile. The incidence rate of all-cause death (per 1000 patient-years) in the propensity-matched cohort of 1016 ChEI users and 1016 non-users was 168.6 in patients on treatment with ChEIs compared with 190.7 in patients not on treatment with ChEIs. In this propensity-matched cohort, treatment with ChEIs was associated with a significantly lower risk of all-cause death (adjusted hazard ratio 0.81, 95% confidence interval 0.71-0.92) and a greater reduction with higher doses of ChEIs. While in the unadjusted analysis, ChEIs were associated with a lower risk of both CV and non-CV death, only the association with non-CV death remained significant after accounting for baseline differences. CONCLUSION: Treatment with ChEIs was associated with a significantly reduced risk of all-cause death, driven by lower rates of non-CV death in a nationwide cohort of patients with previous MI and a diagnosis of AD or mixed dementia. These associations were greater with higher ChEI doses. CONDENSED ABSTRACT: We assessed the association between cholinesterase inhibitors (ChEIs) and clinical outcomes in a nationwide cohort of patients with previous myocardial infarction (MI) and a diagnosis of Alzheimer's disease (AD) or mixed dementi. In propensity-matched analysis, treatment with ChEIs was associated with a 19% reduction in all-cause death driven by non-cardiovascular death. The reduction in all-cause death was greater with the higher doses of ChEIs.

Repeat Mitral Valve Interventions After Transcatheter Edge-to-Edge Repair: The COAPT Trial.

The frequency and effectiveness of repeat mitral valve interventions (RMVI) after transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) are unknown. We aimed to examine the rate of and outcomes after RMVI after TEER in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial. Only 3.9% of COAPT trial patients required a repeat mitral valve intervention during 4-year follow-up which was successful in 90% of cases but was associated with an increased rate of heart failure (HF) hospitalizations (HFH). The COAPT trial randomized HF patients with severe secondary MR to TEER with the MitraClip device plus guideline-directed medical therapy (GDMT) versus GDMT alone. We evaluated the characteristics and outcomes of patients who had an RMVI during 4-year follow-up. A MitraClip implant was attempted in 293 patients randomized to TEER+GDMT, 10 of whom underwent an RMVI procedure (9 repeat TEER and 1 surgical mitral valve replacement) after 4 years of follow-up (cumulative incidence 3.90%, 95% confidence interval [CI] 2.08 to 7.08; median 182 days after the initial procedure). Patients with RMVI had larger mitral annular diameters, fewer clips implanted, and were more likely to have ≥3+MR at discharge compared with those without RMVI. Reasons for RMVI included failed index procedure because of difficult transseptal puncture (n = 2) or tamponade (n = 1); residual or recurrent severe MR after an initially successful procedure (n = 5); partial clip detachment (n = 1); and site-assessed mitral stenosis (n = 1). RMVI was successful in 8/10 (80%) patients. Patients who underwent RMVI had higher 4-year rates of HFH but similar mortality compared with those without RMVI. The annualized incidence rates of all HFH in patients who underwent RMVI were 234 events per 100 person-years (95% CI 139 to 395) pre-RMVI and 46 per 100 person-years (95% CI 25 to 86) post-RMVI as compared with 32 events per 100 patient-years (95% CI 28 to 36) in patients without RMVI. The rate ratio of HFH was reduced after RMVI in patients who underwent RMVI (0.20, 95% CI 0.09 to 0.45). In conclusion, the cumulative incidence of RMVI after 4 years was 3.9% in patients who underwent TEER for severe secondary MR in the COAPT trial. Patients who underwent RMVI were at increased risk of HFH which was reduced after the RMVI procedure. Clinical Trial Registration: Clinical Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier: NCT01626079 URL:https://clinicaltrials.gov/ct2/show/NCT01626079.

Incidence, Predictors, and Impact of Hospital Readmission After Revascularization for Left Main Coronary Disease.

BACKGROUND: The frequency of and relationship between hospital readmissions and outcomes after revascularization for left main coronary artery disease (LMCAD) are unknown. OBJECTIVES: The purpose of this study was to study the incidence, predictors, and clinical impact of readmissions following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for LMCAD. METHODS: In the EXCEL (XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with LMCAD were randomized to PCI vs CABG. The cumulative incidence of readmissions was analyzed with multivariable Anderson-Gill and joint frailty models to account for recurrent events and the competing risk of death. The impact of readmission on subsequent mortality within 5-year follow-up was determined in a time-adjusted Cox proportional hazards model. RESULTS: Within 5 years, 1,868 readmissions occurred in 851 of 1,882 (45.2%) hospital survivors (2.2 ± 1.9 per patient with readmission[s], range 1-16), approximately one-half for cardiovascular causes and one-half for noncardiovascular causes (927 [49.6%] and 941 [50.4%], respectively). One or more readmissions occurred in 463 of 942 (48.6%) PCI patients vs 388 of 940 (41.8%) CABG patients (P = 0.003). After multivariable adjustment, PCI remained an independent predictor of readmission (adjusted HR: 1.22; 95% CI: 1.10-1.35; P < 0.0001), along with female sex, comorbidities, and the extent of CAD. Readmission was independently associated with subsequent all-cause death, with interaction testing indicating a higher risk after PCI than CABG (adjusted HR: 5.72; 95% CI: 3.42-9.55 vs adjusted HR: 2.72; 95% CI: 1.64-4.88, respectively; Pint = 0.03). CONCLUSIONS: In the EXCEL trial, readmissions during 5-year follow-up after revascularization for LMCAD were common and more frequent after PCI than CABG. Readmissions were associated with an increased risk of all-cause death, more so after PCI than with CABG.

Epidemiology, Clinical Characteristics and Cause-specific Outcomes in Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) is a global pandemic affecting 64 million people worldwide. HF with preserved ejection fraction (HFpEF) has traditionally received less attention than its main counterpart, HF with reduced ejection fraction (HFrEF). The incidence and prevalence of HFpEF show geographic variation and are increasing over time, soon expected to surpass those of HFrEF. Morbidity and mortality rates of HFpEF are considerable, albeit lower than those of HFrEF. This review focuses on the burden of HFpEF, providing contemporary data on epidemiology, clinical characteristics and comorbidities, cause-specific outcomes, costs and pharmacotherapy.

Global Public Health Burden of Heart Failure: An Updated Review.

Heart failure (HF) is a rapidly growing public health issue with an estimated prevalence of 64 million people globally. Although the incidence of HF has stabilised worldwide and seems to be declining in developed countries, the prevalence is increasing due to the ageing of the population, improved survival after MI and improved treatment and survival of patients with HF. Yet, HF remains associated with high mortality and morbidity, poor quality of life and functional capacity, and confers a substantial burden to the healthcare system. The prevalence, incidence, mortality and morbidity rates reported show geographical variations, depending on the different aetiologies and clinical characteristics observed among patients with HF. In this review, we provide an overview of the global epidemiology of HF with updated data on prevalence, incidence, mortality and morbidity worldwide.

Impact of Peripheral Artery Disease in Patients With Heart Failure Undergoing Transcatheter Mitral Valve Repair: The COAPT Trial.

Background Peripheral artery disease (PAD) and heart failure (HF) often coexist. Whether PAD influences outcomes of transcatheter mitral valve repair (TMVr) in patients with HF and severe secondary mitral regurgitation is unknown. The objectives are to assess the impact of PAD on outcomes of TMVr plus guideline-directed medical therapy (GDMT) versus GDMT alone in patients with HF and secondary mitral regurgitation. Methods and Results The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized patients with HF with ≥moderate-to-severe secondary mitral regurgitation to TMVr with MitraClip implant plus GDMT versus GDMT alone. We evaluated the relationship between PAD and 2-year outcomes in the COAPT trial and examined whether PAD modified the benefits of TMVr. Among 614 patients enrolled, 109 (17.8%) had PAD. By multivariable analysis, PAD was independently associated with 2-year mortality (adjusted hazard ratio [adjHR], 1.51 [95% CI, 1.07-2.15]) but not HF hospitalizations. Compared with GDMT alone, TMVr reduced the 2-year risk of death in patients without PAD (adjHR, 0.42 [95% CI, 0.30-0.60]) but not those with PAD (adjHR, 1.27 [95% CI, 0.72-2.27]; Pinteraction=0.001). In contrast, TMVr reduced HF hospitalizations consistently in patients with (adjHR, 0.65 [95% CI, 0.35-1.23]) and without (adjHR, 0.42 [95% CI, 0.31-0.57]) PAD (Pinteraction=0.22). Improvements in health status and exercise capacity at 2 years with TMVr compared with GDMT alone were similar in degree, irrespective of PAD status (Pinteraction=0.76 and 0.64, respectively). Conclusions In patients with HF and severe secondary mitral regurgitation, the reduced mortality with TMVr in the overall COAPT study population was not observed in the subgroup of patients with PAD. However, TMVr reduced HF hospitalizations and improved health status and exercise capacity consistently in patients with and without PAD. Registration Clinical Trial Name: Cardiovascular Outocmes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (The COAPT Trial); URL: https://www.clinicaltrials.gov/; Unique identifier: NCT01626079. https://clinicaltrials.gov/ct2/show/NCT01626079.

Minimum Core Data Elements for Transcatheter Mitral Therapies: Scientific Statement by PASSION CV, HVC, and TVTR.

Mitral regurgitation is the most common valvular disease and is estimated to affect over 5 million Americans. Real-world data collection contributes to safety and effectiveness evidence for the U.S. Food and Drug Administration, quality evaluation for the Centers for Medicare and Medicaid Services and hospitals, and clinical best practice research. We aimed to establish a minimum core data set in mitral interventions to promote efficient, reusable real-world data collection for all of these purposes. Two expert task forces separately evaluated and reconciled a list of candidate elements derived from: 1) 2 ongoing transcatheter mitral trials; and 2) a systemic literature review of high-impact mitral trials and U.S multicenter, multidevice registries. From 703 unique data elements considered, unanimous consensus agreement was achieved on 127 "core" data elements, with the most common reasons for exclusion from the minimum core data set being burden or difficulty in accurate assessment (41.2%), duplicative information (25.0%), and low likelihood of affecting outcomes (19.6%). After a systematic review and extensive discussions, a multilateral group of academicians, industry representatives, and regulators established and implemented into the national Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapies Registry 127 interoperable, reusable core data elements to support more efficient, consistent, and informative transcatheter mitral device evidence for regulatory submissions, safety surveillance, best practice development, and hospital quality assessments.

On-Treatment Platelet Reactivity and Ischemic Outcomes in Patients With Diabetes Mellitus: Two-Year Results From ADAPT-DES.

Background Diabetes mellitus and high platelet reactivity (HPR) on clopidogrel are both associated with increased risk of ischemic events after percutaneous coronary intervention, but whether the HPR-associated risk of adverse ischemic events differs by diabetes mellitus status is unknown. Methods and Results ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. HPR was defined as P2Y12 reaction units >208 by the VerifyNow point-of-care assay. Cox multivariable analysis was used to assess whether HPR-associated risk of major adverse cardiac events (MACE; cardiac death, myocardial infarction, or stent thrombosis) varied for patients with insulin-treated diabetes mellitus (ITDM), non-ITDM, and no diabetes mellitus. Diabetes mellitus and HPR were included in an interaction analysis. Of 8582 patients enrolled, 2429 (28.3%) had diabetes mellitus, of whom 998 (41.1%) had ITDM. Mean P2Y12 reaction units were higher in patients with diabetes mellitus versus without diabetes mellitus, and HPR was more frequent in patients with diabetes mellitus. HPR was associated with consistently increased 2-year rates of MACE in patients with and without diabetes mellitus (Pinteraction=0.36). A significant interaction was present between HPR and non-insulin-treated diabetes mellitus versus ITDM for 2-year MACE (adjusted hazard ratio [HR] for non-ITDM, 2.28 [95% CI, 1.39-3.73] versus adjusted HR for ITDM, 1.02 [95% CI, 0.70-1.50]; Pinteraction=0.01). Conclusions HPR was more common in patients with diabetes mellitus and was associated with an increased risk of MACE in both patients with and without diabetes mellitus. In patients with diabetes mellitus, a more pronounced effect of HPR on MACE was present in lower-risk non-ITDM patients than in higher-risk patients with ITDM. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00638794; Unique identifier: NCT00638794. ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).

Prevalence, clinical characteristics and outcomes of heart failure patients with or without isolated or combined mitral and tricuspid regurgitation: An analysis from the ESC-HFA Heart Failure Long-Term Registry.

AIM: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common in patients with heart failure (HF). The aim of this study was to investigate prevalence, clinical characteristics and outcomes of patients with or without isolated or combined MR and TR across the entire HF spectrum. METHODS AND RESULTS: The ESC-HFA EORP HF Long-Term Registry is a prospective, multicentre, observational study including patients with HF and 1-year follow-up data. Outpatients without aortic valve disease were included and stratified according to isolated or combined moderate/severe MR and TR. Among 11 298 patients, 7541 (67%) had no MR/TR, 1931 (17%) isolated MR, 616 (5.5%) isolated TR and 1210 (11%) combined MR/TR. Baseline characteristics were differently distributed across MR/TR categories. Compared to HF with reduced ejection fraction, HF with mildly reduced ejection fraction was associated with a lower risk of isolated MR (odds ratio [OR] 0.69; 95% confidence interval [CI] 0.60-0.80), and distinctly lower risk of combined MR/TR (OR 0.51; 95% CI 0.41-0.62). HF with preserved ejection fraction (HFpEF) was associated with a distinctly lower risk of isolated MR (OR 0.42; 95% CI 0.36-0.49), and combined MR/TR (OR 0.59; 95% 0.50-0.70), but a distinctly increased risk of isolated TR (OR 1.94; 95% CI 1.61-2.33). All-cause death, cardiovascular death, HF hospitalization and combined outcomes occurred more frequently in combined MR/TR, isolated TR and isolated MR versus no MR/TR. The highest incident rates were observed in isolated TR and combined MR/TR. CONCLUSION: In a large cohort of outpatients with HF, prevalence of isolated and combined MR and TR was relatively high. Isolated TR was driven by HFpEF and was burdened by an unexpectedly poor outcome.

Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry.

AIMS: To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). METHODS AND RESULTS: Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. CONCLUSIONS: In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category.

SOdium-glucose CO-transporter inhibition in patients with newly detected Glucose Abnormalities and a recent Myocardial Infarction (SOCOGAMI).

AIMS/HYPOTHESIS: Established dysglycaemia (impaired glucose tolerance [IGT] or type 2 diabetes [T2DM]) is a risk factor for further cardiovascular events in patients with coronary artery disease. Sodium-glucose cotransporter 2 inhibitors reduce this risk. The aim of the present investigation was to test the hypothesis that empagliflozin exerts beneficial effects on myocardial function in patients with a recent acute coronary syndrome and newly detected dysglycaemia. METHODS: Forty-two patients (mean age 67.5 years, 81 % male) with recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected IGT (n = 27) or T2DM (n = 15) were randomised to 25 mg of empagliflozin daily (n = 20) or placebo (n = 22) on top of ongoing therapy. They were investigated with oral glucose tolerance tests, stress-perfusion cardiac magnetic resonance imaging (CMR) and echocardiography at three occasions: before randomisation, after seven months on study drug and three months following cessation of such drug. Primary outcome was a change in left ventricular (LV) end-diastolic volume (LVEDV) and secondary outcomes were a change in a) systolic and diastolic LV function; b) coronary flow reserve; c) myocardial extracellular volume (ECV) in non-infarcted myocardium; d) aortic pulse wave velocity. RESULTS: Empagliflozin induced a significant decrease in fasting and post load glucose (p < 0.05) and body weight (p < 0.01). Empagliflozin did not influence LVEDV, LV systolic or mass indexes, coronary flow reserve, ECV or aortic pulse wave velocity. Echocardiographic indices of LV diastolic function (E/e' and mitral E/A ratio) were not influenced. No safety concerns were identified. CONCLUSIONS/INTERPRETATION: Empagliflozin had predicted effects on the dysglycaemia but did not influence variables expressing LV function, coronary flow reserve and ECV. An explanation may be that the LV function of the patients was within the normal range.

Neutrophil-to-Lymphocyte Ratios in Patients Undergoing Aortic Valve Replacement: The PARTNER Trials and Registries.

Background The neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow-up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5-24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70-4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18-1.63; P<0.0001) compared with those with low NLR, irrespective of treatment modality. In both patients treated with TAVR and patients treated with SAVR, NLR decreased between baseline and 2 years. A 1-unit observed decrease in NLR between baseline and 1 year was associated with lower risk of death or rehospitalization between 1 year and 3 years (aHR, 0.86; 95% CI, 0.82-0.89; P<0.0001). Conclusions Elevated baseline NLR was independently associated with increased subsequent mortality and rehospitalization after TAVR or SAVR. The observed decrease in NLR after TAVR or SAVR was associated with improved outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00530894, NCT0134313, NCT02184442, NCT03225001, NCT0322141.